The Coulter principle or mode of operation is disclosed in Coulter U.S. Pat. No. 2,656,508. This patent discloses an apparatus for counting and classifying particles suspended in an electrically conducting liquid. Two containers or vessels are in fluid communication with one another through a microscopically small measuring aperture. The passage of a microscopic particle suspended in the conducting liquid of one container through the aperture whose dimensions approximate those of the particles causes a change in the resistance of the electric path through the liquid effectively contained in the aperture, assuming that the material of the particle in the liquid has an electrical conductivity different from that of the liquid. Suitable electrodes in the two containers are immersed in the conducting liquid on both sides of the aperture and are connected to an electrical current source and measuring circuit. The change in electrical resistance results in a change in electrical current flowing through the liquid as the particle moves through the aperture. The magnitude of the change in electrical resistance (or voltage) is a measure of the size of the particle moving through the aperture.
Variations of the apparatus disclosed in the Coulter U.S. Pat. No. 2,656,508 appear in U.S. Pat. Nos. 3,710,933; 3,259,842; 3,793,587; 3,924,180; 3,944,917; 4,019,134 and East German Pat. No. 66,038.
U.S. Pat. No. 3,793,587 discloses two spaced-apart measuring apertures of different dimensions arranged in tandem, whereby a particle volume measurement may be obtained at one measuring aperture and a particle cross-section measurement may be obtained at the other measuring aperture. Two apertures of different geometry are essential to the operation of the system disclosed in this patent. One aperture must be long enough to contain in the region of uniform field strength the entire volumes of the particles moving through it, while the other aperture has a shorter length to evaluate essentially particle cross-sections.
U.S. Pat. Nos. 3,924,180 and 4,019,134 both disclose apparatus for electrically analyzing biological cells wherein an orifice having two potential sensing electrodes is immersed in the container of the electrically conducting liquid in which the cells or particles to be analyzed are suspended. The orifice is positioned adjacent and aligned with the aperture in the other container, whereby the entrance to the orifice communicates with the particle suspension and the exit of the orifice communicates with the aforesaid aperture for evacuating the cell or particle containing liquid through the orifice and aperture.
East German Pat. No. 66,038 discloses a lamination of dielectric bodies and alternately appearing metal electrodes constituting one-half of an assembly through which particles are designed to pass. The other half of the assembly is a cover in the form of a single integral block of insulation. A conduit passes through the assembly between the two halves. In one embodiment described in the patent pin-like electrodes protrude or jut into the conduit. No suggestion appears in the patent for the need of a smooth hydrodynamic flow path for the particles passing through the conduit.
The foregoing patents provide the prior art background for an understanding of the operation of the Coulter system of which the present invention is an outgrowth. The descriptions in these patents are to be considered as though bodily incorporated herein.
A problem encountered in particle counting and analyzing apparatus operating on the Coulter principle of the type described, for example, in U.S. Pat. Nos. 3,924,180 and 4,019,134, is the noise due to the Johnson effect (thermal noise due to random motion of charges in the conductive liquid or electrolyte). This random noise places a limit on the smallest size of the particle which can be counted and analyzed by the apparatus.
U.S. Pat. No. 4,019,134 discloses a multiple sensing electrode flow cell, but does not have multiple particle sensing zones and is used to make the signals independent of the liquid conductivity.